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Record W4292865371 · doi:10.1038/s41591-022-01925-w

Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

2022· article· en· W4292865371 on OpenAlexaff
Marta Milà‐Alomà, Nicholas J. Ashton, Mahnaz Shekari, Gemma Salvadó, Paula Ortiz‐Romero, Laia Montoliu‐Gaya, Andréa Lessa Benedet, Thomas K. Karikari, Juan Lantero‐Rodriguez, Eugeen Vanmechelen, Theresa A. Day, Armand González‐Escalante, Gonzalo Sánchez‐Benavides, Carolina Minguillón, Karine Fauria, José Luís Molinuevo, Jeffrey L. Dage, Henrik Zetterberg, Juan Domingo Gispert, Marc Suárez‐Calvet, Kaj Blennow

Bibliographic record

VenueNature Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsMcGill University
FundersNational Institute on AgingNational Research, Development and Innovation OfficeNational Institutes of HealthOlav Thon StiftelsenEuropean Federation of Pharmaceutical Industries and AssociationsUK Dementia Research InstituteVetenskapsrådetFamiljen Erling-Perssons StiftelseEuropean CommissionHjärnfondenMinisterio de Economía y CompetitividadBundesministerium für Bildung und ForschungFonds National de la Recherche LuxembourgUniversity College LondonVlaamse regeringMinisterio de Ciencia, Innovación y UniversidadesEU Joint Programme – Neurodegenerative Disease ResearchInstituto de Salud Carlos IIIAlzheimer's Drug Discovery FoundationZonMwAlzheimer's AssociationStiftelsen för Gamla TjänarinnorAgentschap Innoveren en OndernemenEli Lilly and Company
KeywordsMedicinePathologyDiseasePositron emission tomographyAlzheimer's diseasePopulationAmyloid (mycology)BiomarkerInternal medicineCohortOncologyBiologyNuclear medicine

Abstract

fetched live from OpenAlex

Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer's disease clinical trials.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.113
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.371
Teacher spread0.342 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations349
Published2022
Admission routes1
Has abstractyes

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